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首页> 外文期刊>International Journal of Molecular Sciences >BMP3 Alone and Together with TGF-β Promote the Differentiation of Human Mesenchymal Stem Cells into a Nucleus Pulposus-Like Phenotype
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BMP3 Alone and Together with TGF-β Promote the Differentiation of Human Mesenchymal Stem Cells into a Nucleus Pulposus-Like Phenotype

机译:单独的BMP3并与TGF-β一起促进人间充质干细胞分化为髓核样表型

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Human mesenchymal stem cells (MSCs) have the potential to differentiate into nucleus pulposus (NP)-like cells under specific stimulatory conditions. Thus far, the effects of bone morphogenetic protein 3 (BMP3) and the cocktail effects of BMP3 and transforming growth factor (TGF)-β on MSC proliferation and differentiation remain obscure. Therefore, this study was designed to clarify these unknowns. MSCs were cultured with various gradients of BMP3 and BMP3/TGF-β, and compared with cultures in basal and TGF-β media. Cell proliferation, glycosaminoglycan (GAG) content, gene expression, and signaling proteins were measured to assess the effects of BMP3 and BMP3/TGF-β on MSCs. Cell number and GAG content increased upon the addition of BMP3 in a dose-dependent manner. The expression of COL2A1, ACAN, SOX9, and KRT19 increased following induction with BMP3 and TGF-β, in contrast to that of COL1A1, ALP, OPN, and COMP. Smad3 phosphorylation was upregulated by BMP3 and TGF-β, but BMP3 did not affect the phosphorylation of extracellular-signal regulated kinase (ERK) 1/2 or c-Jun N-terminal kinase (JNK). Our results reveal that BMP3 enhances MSC proliferation and differentiation into NP-like cells, as indicated by increased cell numbers and specific gene expressions, and may also cooperate with TGF-β induced positive effects. These actions are likely related to the activation of TGF-β signaling pathway.
机译:人间充质干细胞(MSC)具有在特定刺激条件下分化为髓核(NP)样细胞的潜力。到目前为止,骨形态发生蛋白3(BMP3)的作用以及BMP3和转化生长因子(TGF)-β对MSC增殖和分化的混合效应仍然不清楚。因此,本研究旨在澄清这些未知因素。用各种梯度的BMP3和BMP3 /TGF-β培养MSC,并与基础和TGF-β培养基中的培养进行比较。测量细胞增殖,糖胺聚糖(GAG)含量,基因表达和信号蛋白,以评估BMP3和BMP3 /TGF-β对MSC的影响。加入BMP3后,细胞数量和GAG含量以剂量依赖性方式增加。与COL1A1,ALP,OPN和COMP相比,BMP3和TGF-β诱导后,COL2A1,ACAN,SOX9和KRT19的表达增加。 BMP3和TGF-β上调了Smad3的磷酸化,但BMP3并不影响细胞外信号调节激酶(ERK)1/2或c-Jun N-末端激酶(JNK)的磷酸化。我们的研究结果表明,BMP3可增强MSC增殖和分化为NP样细胞,如增加的细胞数量和特定基因表达所示,并且还可能与TGF-β诱导的阳性作用协同作用。这些作用可能与TGF-β信号通路的激活有关。

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